In silico pharmacology最新文献

{"title":"Exploring the therapeutic potential of <i>Premna barbata</i> Wall. ex Schauer stem bark in colon cancer: apoptosis induction, cell cycle analysis, and in-silico insights.","authors":"Bhuwan Chandra Joshi, Vijay Juyal, Archana N Sah, Supriyo Saha, Minky Mukhija","doi":"10.1007/s40203-025-00379-5","DOIUrl":"10.1007/s40203-025-00379-5","url":null,"abstract":"<p><p><i>Premna barbata</i> Wall. ex Schauer (<i>P. barbata</i>) is a deciduous shrub with immense folkloric uses. Based on the previous anticancer screening, we identified that the extract showed potent activity against the human cancer cell line. The present investigation was conducted using the ethyl acetate extract of the stem bark of <i>P. barbata</i> to unravel its cytotoxicity, induction of apoptosis, and cell cycle analysis progression in colon cancer cell lines. The plant material was extracted with petroleum ether followed by ethyl acetate. Here we performed apoptosis assay and cell cycle analysis against human cancer (COLO-205) cell line, followed by quantitative analysis of the extract by High-performance liquid chromatography (HPLC), High-performance thin layer chromatography (HPTLC) fingerprinting to identify the presence of possible active constituents, and then perform molecular docking interaction study of the constituent against receptors related to colon cancer. 20 ns MD simulation was performed against the top 3 docked receptors using GROMACS software. HPLC of the extract showed the presence of rutin as an active compound. The HPTLC analysis revealed the presence of 5.30% w/w rutin. Rutin had remarkable inhibitory activities against human cancer cell lines. Molecular docking studies of rutin against colon cancer receptors showed that rutin has a maximum docking score of (- 10.2 kcal/mol) against nitric oxide synthase. Molecular dynamic analysis of rutin in complexes with colon cancer receptors suggested a stable binding behavior and interaction. Overall, our results reveal that the <i>P. barbata</i> stem bark extract is a potential candidate for the development of future cancer chemotherapeutics.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"93"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking of <i>Berberis asiatica</i>-derived compounds targeting DDX3 DEAD BOX RNA helicase of <i>Leishmania donovani</i>.","authors":"Vinita Gouri, Ketki Patne, Sumeet Singh, Akanksha Kanojia, Rohini Muthuswami, Mukesh Samant","doi":"10.1007/s40203-025-00377-7","DOIUrl":"10.1007/s40203-025-00377-7","url":null,"abstract":"<p><p>Visceral leishmaniasis (VL), caused by <i>Leishmania donovani</i>, continues to pose a significant global health burden, especially in tropical and subtropical regions. Current therapeutic options are limited by toxicity, high cost, and emerging drug resistance, necessitating the discovery of novel, safer alternatives. In this study, molecular docking approaches were used to identify potential inhibitors of LdHEL-67, a crucial DEAD-box RNA helicase (DDX3 family) in <i>L</i>. <i>donovani</i>. A total of 100 bioactive compounds were identified through GC-MS analysis of ethanol and hexane extracts of <i>Berberis asiatica</i>, of which 48 compounds were selected based on their percentage occurrence in extracts. These compounds were initially docked against LdHEL-67 and its human homolog (PDB ID: 6CZ5) using PyRx for comparative analysis. To enhance reliability, all 48 compounds were re-docked using AutoDock, and 14 compounds with the highest binding affinities were shortlisted for further evaluation. For example, Compound 21 exhibited binding energies of - 11.7 kcal/mol (AutoDock) and - 6.5 kcal/mol (PyRx), while Compound 47 showed - 11.4 kcal/mol and - 7.5 kcal/mol, respectively. Cavity detection using CavityPlus predicted one prominent druggable pocket each for LdHEL-67 and its human counterpart, into which the top 14 compounds were subsequently docked. Top 14 compounds analysed for ADMET and toxicity prediction. <i>In-vitro</i> assays using ethanol and hexane extracts demonstrated significant anti-promastigote activity against <i>L. donovani</i> with minimal cytotoxicity to THP-1-derived macrophages. These results highlight the therapeutic potential of <i>B. asiatica</i>-derived compounds and support further exploration of LdHEL-67 as a promising drug target for VL treatment.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00377-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"92"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual screening and molecular dynamic simulations of <i>Desulfovibrio vulgaris</i> dissimilatory sulfite reductase inhibitors for the control of sulphate reducing bacteria.","authors":"Oluwafemi Adebayo Oyewole, Rahma Muhammad Adamu, Umar Saidu, Sekelwa Cosa, Mthokozisi B C Simelane, Md Atiar Rahman, Mohammed Auwal Ibrahim","doi":"10.1007/s40203-025-00367-9","DOIUrl":"10.1007/s40203-025-00367-9","url":null,"abstract":"<p><p>Dissimilatory sulfite reductase (DSR) plays a crucial role in the metabolism of sulfate-reducing bacteria (SRB), which contribute to environmental hazards such as biocorrosion and sulfide pollution. The search for effective DSR inhibitors has been challenging due to the difficulty in culturing strict anaerobes. In this study, we employed molecular docking and 100 ns molecular dynamics (MD) simulations to screen 248 microbially-derived compounds for their potential as DSR inhibitors. Based on docking scores, nine hit compounds were identified, with dehydrocitreaglycon A exhibiting the highest binding affinity (-9.4 kcal/mol), followed by citreamicin theta A and etamycin. Hydrogen bond interaction analysis revealed that key active site residues, including Arg83, Arg101, and Lys215, played significant roles in ligand binding. MD simulations revealed varying stability among the DSR-compound complexes, with arisugacin A demonstrating the highest stability and minimal fluctuations, while antimycin A1 and peniciadametizine A showed the highest instability. The principal component analysis (PCA) indicated greater conformational flexibility in complexes with antimycin A1, etamycin, citreamicin theta A, and terretonin G. Binding free energy calculations confirmed that dehydrocitreaglycon A (-112.13 kJ/mol) and strobilurin (-107.66 kJ/mol) had the most favorable interactions with DSR. Furthermore, an in silico environmental toxicity assessment indicated that some compounds, such as salmochelin sx, posed higher toxicity risks, whereas others, like dehydrocitreaglycon A, showed lower environmental impact. Overall, our findings highlight strobilurin, arisugacin A, and dehydrocitreaglycon A as promising DSR inhibitors, warranting further investigation for potential applications in SRB control.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00367-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"90"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amlodipine protects the retinal ganglionic cell damage maintaining intra ocular pressure by regulating the biological activities of carrageenan like red algae: an in vivo and in-silico study.","authors":"AshIrbad Nanda, Neha Choudhary, Manorama Patri","doi":"10.1007/s40203-025-00381-x","DOIUrl":"10.1007/s40203-025-00381-x","url":null,"abstract":"<p><p>Carrageenan (Carr), a natural polysaccharide derived from edible red algae, was used for the green biosynthesis and also recognized as toxic compound causing oxidative stress. The objective was to know the insight mechanism of Carr-induced retino ganglionic cell (RGCs) damage and its connection with brain having two model systems, mammalian (rabbit), lower vertebrates (zebrafish). The present study investigated the modulatory effect of amlodipine (AML), a dihydropyridine calcium channel antagonist, against Carr-induced RGCs loss. AML and Carr were analyzed through in silico study to predict their protein targets and infer their drug-target interactions with glaucoma. AML demonstrated strong binding affinity with differentially expressed glaucoma targets of Carr, specifically N-formyl peptide receptor, N-type calcium channel and sodium channel protein type, suggesting a clue towards the link with the regulatory role of AML. The neuronal damage in RGCs layer was clearly observed through histopathological study in Carr-treated zebrafish while amlodipine co-administration with Carr shown to decrease the percentage of pycknotic cell count in zebrafish brain. A 40% decrease in IOP was observed after exposure to topical AML in the normotensive rabbit eye after carrageenan treatment, with IOP returning to baseline by 300 min. In conclusion, the present study involving in silico and in vivo analysis demonstrated that AML has protective role against carr-induced oxidative stress promoting RGC degeneration with IOP lowering property. Identification of AML like pharmacologic modulators is needed to develop new therapeutic targets for visual system disorders.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00381-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"91"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA seq data analysis reveals molecular markers and possible treatment targets for laryngeal squamous cell carcinoma (LSCC): an in-silico approach.","authors":"Md Hasan Jafre Shovon, Partha Biswas, Md Imtiaz, Shirajut Mobin, Md Nazmul Hasan","doi":"10.1007/s40203-025-00382-w","DOIUrl":"10.1007/s40203-025-00382-w","url":null,"abstract":"<p><p>Laryngeal squamous cell carcinoma (LSCC), a complex cancer driven by genetic mutations, poses significant challenges for detection and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as a promising tool to uncover the cellular heterogeneity in cancer and identify novel therapeutic targets. In this study, we used scRNA-seq data (GSE252490) to explore molecular biomarkers for LSCC diagnosis and treatment. After processing and standardizing the data, we performed principal component analysis to identify highly variable genes. Cell clustering revealed 12 distinct clusters with unique molecular features. Differential gene expression analysis identified 6434 differentially expressed genes (DEGs), which were further analyzed using gene ontology enrichment to explore biological processes involved in LSCC progression. Protein-protein interaction (PPI) network analysis revealed 20 central genes associated with key cancer pathways. Pathway enrichment analysis through KEGG highlighted the involvement of these genes in various cancer-related pathways. Notably, genes such as CCL3, EPCAM, and IL8, with elevated expression, were linked to survival outcomes in LSCC. This comprehensive analysis provides valuable insights into the molecular landscape of LSCC, identifying potential biomarkers and therapeutic targets for improved diagnosis and treatment.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"89"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of approved drugs towards Nipah virus treatment: an in silico docking, molecular dynamics simulation and a MM/GBSA approach.","authors":"Madushmita Hatimuria, Jyoti Vishwakarma, Dineshbabu Takkella, C Nikesh Chandran, Plabana Phukan, Krishna Gavvala, Ashok Pabbathi","doi":"10.1007/s40203-025-00371-z","DOIUrl":"10.1007/s40203-025-00371-z","url":null,"abstract":"<p><p>The Nipah virus (NiV) is an emerging zoonotic pathogen that causes severe febrile encephalitis, transmitted from infected animals to humans. Since its initial outbreak in Malaysia, subsequent epidemics have occurred across Asia, including India, with mortality rates ranging from 40 to 75%. There are no approved vaccines, or antiviral treatments currently exist for NiV infections. In this study, molecular docking was conducted using 42 FDA-approved drugs targeting the Nipah virus glycoprotein-human receptor complex. Binding affinities and 2D interaction profiles were analyzed, revealing five promising candidates: Saquinavir, Nelfinavir, Simeprevir, Paritaprevir, and Tipranavir. These compounds exhibited strong binding affinities, ranging from - 9.8 to -11.1 kcal/mol. These five top potential drugs were subjected to molecular dynamics (MD) simulations for 200 ns to further assess their stability, flexibility and compactness. MM/GBSA analysis was employed to estimate their binding free energies. The MD simulations confirmed their favourable binding properties, demonstrating significant stability and minimal fluctuation during the stability. Subsequently, drug-likeness evaluations were performed to assess key pharmacokinetic parameters, including absorption, distribution, metabolism, excretion, and toxicity (ADMET), with an emphasis on toxicity prediction and drug-like properties. The results revealed stable interactions with minimal structural fluctuations, supporting their potential as repurposed therapeutics for Nipah virus infection. To evaluate their efficacy and contribute to the development of effective antiviral treatments against NiV, further in vivo testing in animal models and human trials is recommended.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00371-z.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"86"},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational study of phytochemicals from Khaya grandifoliola (WELW) as potential inhibitors of the <i>Plasmodium falciparum</i> transketolase and putative antimalarial agents.","authors":"Joseph M Agbedahunsi, Mojisola C Cyril-Olutayo, Racheal Y Fadare, Frank A Ogundolie, Deeksha Salaria, Rajan Rolta, Samuel A Idowu, Ayomide B Oladele, Praise D Eso, Esther O Olatunji, Olatomide A Fadare","doi":"10.1007/s40203-025-00378-6","DOIUrl":"10.1007/s40203-025-00378-6","url":null,"abstract":"<p><p>The tropical and subtropical region has been challenged with Malaria; a life-threatening disease caused by <i>Plasmodium falciparum</i>. The rise of anti-malarial drug resistance, especially drug resistant <i>Plasmodium falciparum</i> strains has led to the urgent need for novel antimalarial drugs. This study focuses on using computational techniques to investigate and profile phytochemicals found in <i>K. grandifoliola,</i> a plant known for its medicinal use in Africa for treating malaria in particular, as potential inhibitors of the <i>Plasmodium falciparum</i> transketolase enzyme and putative antimalarial agents. Computational techniques, including molecular docking and molecular dynamics simulations, were employed to assess the binding affinity, stability, and interactions of the identified phytochemicals with the target protein. The findings revealed that three phytochemicals, Khivorin (AKT-6), 7-deacetylkhivorin (AKT-18), and 1-deacetylkhivorin (AKT-22), exhibited favorable pharmacokinetic properties, drug-likeness, and strong binding affinity for the <i>P. falciparum</i> transketolase. Molecular dynamics simulations confirmed the stability of the protein-ligand complexes, further supporting the potential of these compounds as inhibitors. The identified phytochemicals that demonstrated significant binding potential and stability upon forming complex with transketolase, having optimum pharmacokinetics, suggests their potential as lead compounds for future drug discovery efforts.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"87"},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico identification of novel inhibitors of human androgen receptors and prostrate-specific membrane antigen: a comprehensive target-based molecular docking, molecular dynamics simulation, and ADME-toxicity studies.","authors":"Adejoke Oluwaseun Osideko, Ibrahim Olaide Adedotun, Misbaudeen Abdul-Hammed, Suleiman Temitayo Badmos","doi":"10.1007/s40203-025-00375-9","DOIUrl":"10.1007/s40203-025-00375-9","url":null,"abstract":"<p><p>Prostate cancer (PC) remains a deadly disease that requires urgent attention. It's the second most frequent cancer type that affects men globally, with over 1.4 million cases and 358,989 deaths recorded so far. Despite the several available treatment options ranging from surgery (prostatectomy) to chemo- and radiation therapy for PC patients, associated side effects such as risk of excessive bleeding after treatment, erectile dysfunction, risk of infertility, and incontinence, among others, necessitate the need for a safer and highly effective anti-prostate cancer medication, especially from natural sources. Thus, the current study examines eighty-three isolated compounds from <i>Rauwolfia vomitoria</i> as potential anti-prostate cancer medication using a computer-aided drug design (CADD) approach. The choice of <i>Rauwolfia vomitoria</i> is due to its reported medicinal value. Researchers have explored this utility plant to treat numerous health challenges, including cancer. Thus, the isolated compounds (ligands) were docked against prostate cancer drug targets with PDB IDs 1XOW and 2XEI using the Pyrx docking tool. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the selected ligands were analyzed using the admetSAR3.0 tool. In contrast, SwissADME was used to analyze the drug-likeness and bioavailability of the selected ligands, including other physicochemical properties, binding modes, and molecular interactions. The molecular dynamics simulation of the identified lead and PC standard drug was carried out using GROMACS 2018. 3 software, while trajectories were analyzed using GROMACS modules, and all plots were done using the Xmgrace tool. The result of all these operations identified L4 (cholesterol-3-13C) and L80 (stigmasterol) as novel lead compounds against the two prostate cancer drug targets (1XOW and 2XEI), which have not been reported earlier to the best of our knowledge. The binding affinities of both leads are (- 8.2 kcal/mol and - 9.8 kcal/mol for L4 against 1XOW and 2XEI, respectively) and (- 9.0 kcal/mol and - 9.1 kcal/mol for L80 against 1XOW and 2XEI, respectively). The identified lead possessed excellent ADMET properties, bioactivities, and drug-likeness and interacted effectively with the target sites. The molecular dynamics simulation studies of the identified ligand also confirmed their stability in the active site of the drug targets. Therefore, these leads could be optimized and developed towards the development of novel therapeutic agents against prostate cancer.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"88"},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive In-silico analysis of the known and novel synthesized 5-substituted barbituric acid derivatives acting as CNS depressants.","authors":"Soni Rani, Manisha Behera, Soma Mondal Ghorai, Gagandeep Singh","doi":"10.1007/s40203-025-00376-8","DOIUrl":"10.1007/s40203-025-00376-8","url":null,"abstract":"<p><p>Anaesthetics such as barbiturates function as inhibitory-neurotransmitters by attaching to the accessible pockets of the GABA_A receptors, which function through ligand-gated Cl^- channels. This study investigates the interaction dynamics between various barbiturate analogues and GABA_A receptors to identify potential alternatives to phenobarbital with improved therapeutic profiles. The comprehensive ADME/TOX assessments, molecular docking studies, molecular dynamic analysis, binding free energy calculations, and Ion Channel Analysis using Channel Annotation Package were performed to examine the interaction of phenobarbital, 2-thiobarbiturate, and several spirobarbiturate derivatives with GABA_A receptors. Our findings reveal that molecular docking alone does not predict therapeutic efficacy in modulating chloride transport. Although spirobarbiturates demonstrated strong interactions (particularly methoxy-SB at - 53.20 kcal/mol compared to phenobarbital's - 31.22 kcal/mol), they exhibited suboptimal pharmacokinetic properties, with molecular weights exceeding 500 g/mol, limiting their bioavailability. Notably, 2-thiobarbiturate emerged as the most promising candidate despite its relatively weaker binding affinity (- 27.70 kcal/mol), as it demonstrated stable interactions with all GABA_A receptor chains, superior intestinal and blood-brain barrier permeability, excellent bioavailability, and minimal toxicity concerns. These results challenge the conventional approach of prioritizing high binding affinity in drug discovery and highlight the importance of balancing moderate binding with optimal channel functionality and favourable ADME/TOX properties. 2-Thiobarbiturate represents a potentially safer alternative to phenobarbital, which is currently classified as a drug of abuse, offering new possibilities for the development of mild antidepressants and hypnotic medications.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"82"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-driven docking of diverse DDAs as promising cysteine protease inhibitors targeting Mpox virus.","authors":"Bader S Alotaibi, Irfan Ahmad, Bandar Almutairy, Abdullah Alkhammash, Ahad Amer Alsaiari, Kanwal Khan, Samiullah Burki","doi":"10.1007/s40203-025-00374-w","DOIUrl":"10.1007/s40203-025-00374-w","url":null,"abstract":"<p><p>The rise of zoonotic viruses like Monkeypox (mpox) presents significant challenges to public health, the economy, and modern medical practices. These pathogens, which can transfer from animals to humans, have the potential to cause both localized outbreaks and global pandemics. Monkeypox, recently recognized as a zoonotic virus, is particularly concerning due to its severe impact, especially on children and those with weakened immune systems. In light of the pressing need for effective treatments, repurposing existing drugs and utilizing computational modeling have emerged as vital strategies for discovering potential therapeutic agents. Research has demonstrated the promise of Direct Acting Antivirals (DAAs) against various viral infections. By employing computational tools and existing data, we can quickly identify potential treatments to combat the current mpox outbreak. Given that the cysteine protease of mpox bears similarities to proteases found in viruses such as HCV and HIV, it is plausible that DAAs could inhibit mpox protease. We applied machine learning techniques, including Support Vector Machines (SVM), Reinforcement Learning (RL), and K-Nearest Neighbors (KNN), to analyze a set of 86 DAAs. The compounds predicted to be effective inhibitors were then assessed using structural modeling methods. Our docking simulations identified four DAAs-Paritaprevir (DB09297), Ledipasvir (DB09027), Lenacapavir (DB15673), and Bictegravir (DB11799)-as having particularly strong binding affinities for mpox protease. Key interacting residues, such as Cys328, Tyr270, His241, and Gly329, were found to be critical in the binding process. These results indicate that FDA-approved DAAs might provide new treatment avenues for mpox. Nevertheless, additional validation through experimental studies is necessary to confirm the biological effectiveness of these drug candidates. This research provides a foundational basis for exploring DAAs as potential new treatments for mpox, with future investigations required to fully determine their therapeutic value.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00374-w.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"85"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}